While fibroblast growth factor (FGF) 1 is expressed in multiple tissues, only adipose-derived and brain FGF1 have been implicated in the regulation of metabolism. Adipose FGF1 production is upregulated in response to dietary stress and is essential for adipose tissue plasticity in these conditions. Similarly, in the brain, FGF1 secretion into the ventricular space and the adjacent parenchyma is increased after a hypercaloric challenge induced by either feeding or glucose infusion. Potent anorexigenic properties have been ascribed to both peripheral and centrally injected FGF1. The ability of recombinant FGF1 and variants with reduced mitogenicity to lower glucose, suppress adipose lipolysis and promote insulin sensitization elevates their potential as candidates in the treatment of type 2 diabetes mellitus and associated comorbidities. Here, we provide an overview of the known metabolic functions of endogenous FGF1 and discuss its therapeutic potential, distinguishing between peripherally or centrally administered FGF1. Gasser et al. provide a concise overview of the known metabolic functions of endogenous FGF1 and discuss its therapeutic potential after peripheral or central administration.